(Section A: Virology) Lecture 05: Virus Entry

Question 1

State:

Concept of Virus Entry

Answer 1

1. Recognition of host receptor (attachment)
2. Mechanism to release genome (eg. in the cytoplasm)

Question 2

True or False:

Viruses can passively diffuse through the cell membrane

Answer 2

False, they are too large to be passively transported through the host cell membrane

Question 3

KEY CONCEPT:

The virion must be….

Answer 3

Stable and unstable
* Varies during different times of infectious cycle

Question 4

Do random electrostatic interactions by the virus with host cells initiate infectious cycle?

Answer 4

No

Question 5

What do interactions with the receptor allow a virus to do?

Answer 5

“Opens the door” for the virus, allows virus to release genome inside host

Question 6

True or False:

Host cell receptors recognize viruses

Answer 6

True

Question 7

Define:

Co-receptor

Answer 7

Sometimes viruses require a second receptor in order to enter a host cell

Question 8

There are a variety of host cell receptors, what are characteristics shared by all of them?

Answer 8

1. All are surface membrane proteins
2. Same receptor can recognize more than 1 virus

Question 9

Define:

PVR

Answer 9

Polio virus receptor

Question 10

Define:

ACE2

Answer 10

Angiotensin-Converting Enzyme 2 receptor
* SARS CoV2 receptor

Question 11

Define:

CD46

Answer 11

Cell viral receptor for Measles Virus

Question 12

Define:

LDL Receptor

Answer 12

Host cell viral receptor for Rhinoviruses (common cold etc.)

Question 13

Why are there two different modes of attachment for viruses?

Answer 13

Viruses can be non-enveloped hard shell virus or enveloped virus

Question 14

Describe:

Entry for a non-enveloped virus with icosahedral symmetry

(use a virus for example)

Answer 14

Picornaviridae - Poliovirus
* ssRNA (+) virus, ready-to-go
* Has viral proteins 1, 2, 3

Steps:
* VP1 interacts with PVR
* At least 2 interactions at a time
* Interacts directly with the plasma membrane
* Creates conformation change
* Hydrophobic N-termini of VP1 insert into membrane, results channel for genome entry

Question 15

Describe:

Entry for an enveloped virus

(use a virus for example)

Answer 15

Influenza virus
* ssRNA (-), has to make RNA (+)
* Has hemagglutinin

Heamgglutinin binds to host cell receptors
* Interacts with Sialic Acid

Question 16

Describe:

Sialic acid mechanism

Answer 16

Sialic acid attaches to galactose, resulting in two possible forms:
* 2-3 carbon linkage (mostly in upper respiratory tract)
* 2-6 carbon linkage (mostly in lower respiratory tract)

Question 17

Compare:

Human influenza and Avian influenza

(in terms of virus entry)

Answer 17

Human influenza
* Prefer 2-6 linkages
* Infects upper respiratory tract

Avian influenza
* Prefer 2-3 linkages
* Infects lower respiratory tract (lungs)

Question 18

Early CoV2 infected lower respiratory tract. What are trademarks of this?

Answer 18

Slow appearance of symptoms (takes long time for virus to get in and replicate)
* Severe symptoms

Question 19

Omicron variants of CoV2 infected the upper respiratory tract. What was a trademark of this?

Answer 19

Quick appearance of symptoms
* Not severe, as it only infects upper respiratory tract
* More infectious

Question 20

Virus enter the cell via…

Answer 20

Common cellular mechanisms

Question 21

What are some common cellular mechanisms for entry?

Answer 21

• Phagocytosis
• Pinocytosis
• Receptor-mediated endocytosis

Question 22

What are the 3 forms of cellular entry mechanisms we study known as?

Answer 22

Endocytosis (happens at surface of cell)

Question 23

True or False:

Endocytosis is passive transport

Answer 23

False, it is active transport

Question 24

Give an analogy for:

Cell entrance mechanisms

Answer 24

Transport vesicles “move” along tracks that are powered by molecular motors

Question 25

Define:

Release

Answer 25

A trigger that releases virus or genomic contents in the cytoplasm

Question 26

Where can genomic “release” occur?

Answer 26

1. Right at the cell surface
2. Early endosome
3. Late endosome

Question 27

State:

pH of different locations of release

Answer 27

1. Cell surface: 7.0 pH
2. EE: 6.5-6.0 pH
3. LE: 5.5-5.0 pH

Question 28

Describe:

Reovirus entry

Answer 28

Has a hard shell, dsDNA
* Like an “onion”, multilayered

1. pH at EE causes loss of capsid
2. Cystein proteases at LE begin to cut into the virus
3. Virus is ready to release genome

Question 29

What are cystein proteases? Are they host or virus?

Answer 29

Cathepsins
* They are host cell proteins
* Active in late endosome

Question 30

Describe:

Paramyxoviridae (Measles virus) entry

Answer 30

Enveloped virus
* Goes through fusion events

Viral proteins mediate fusion events
* Behave differently depending on the specific pH

Question 31

Describe:

Viral fusion event

(use influenza virus example)

Answer 31

• Proteins are originally packed down
• Gets protonated, causes viral proteins to “stretch out”
• Links to host cell membrane
• Pulls in the membrane and creates channel for genome to enter

Question 32

What is unique about Ebola virus?

Answer 32

Ebola virus performs fusion event that is pH dependent

Injects genome at late endosome
* Attaches to NPC1 receptor (lipid transporter)
* A sugar blocks viral receptor (GP1/GP2)
* When eliminated by cathepsins, allows ebola virus to attach to NPC1 and enter

Question 33

True or False:

NPC1 is a cell surface receptor

Answer 33

False, it is a late endosome receptor